tbuckley/cabot-search huggingface dataset:
Phase III MIRASOL (GOG 3045/ENGOT-ov55) study: Initial report of mirvetuximab soravtansine vs. investigator's choice of chemotherapy in platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression.
Authors: Kathleen N. Moore, Antoine Angelergues, Gottfried E. Konecny, Susana N. Banerjee, Sandro Pignata, Nicoletta Colombo, John William Moroney, Casey Cosgrove, Jung-Yun Lee, Andrzej Roszak, Shani Breuer, Jacqueline Maria Tromp, Diana Bello-Roufai, Lucy Gilbert, Rowan Miller, Tashanna K. N. Myers, Yuemei Wang, Anna Berkenblit, Domenica Lorusso, Toon Van Gorp
Journal: Journal of Clinical Oncology (2023)

LBA5507 Background: Mirvetuximab soravtansine (MIRV), an antibody drug conjugate targeting FRα, demonstrated clinically meaningful antitumor activity in a single arm trial reported previously (Matulonis, JCO 2023). MIRASOL is a randomized phase 3 trial to confirm the efficacy of MIRV vs standard-of-care chemotherapy in patients (pts) with PROC. Methods: 453 PROC pts with high FRα expression (Roche FOLR1 Assay) with 1-3 priors were randomized 1:1 to MIRV 6 mg/kg, adjusted ideal body weight, Day 1 of a 21-day cycle or IC: paclitaxel, pegylated liposomal doxorubicin, or topotecan. The primary efficacy endpoint was progression-free survival (PFS) by investigator (INV) with key secondary endpoints ORR, overall survival (OS), and patient-reported outcomes in hierarchical order; other endpoints included safety and tolerability. Blinded independent central review (BICR) for PFS and ORR were sensitivity analyses. Results: With a data cutoff of March 6, 2023, 227 pts were randomized to the MIRV arm; 226 to the IC arm. Median follow-up was 13.1 months. Baseline characteristics were well balanced across arms; 14% of pts had one, 39% two, and 47% three prior lines of therapy; 62% received prior bev; and 55% received prior PARPi therapy. The study met its primary and key secondary endpoints with statistically significant results in PFS (INV), ORR (INV), and OS (Table). In the bev-pretreated subset (n=281), PFS HR was 0.64 (0.492, 0.842) and OS HR was 0.74 (0.535, 1.036); in the bev-naïve subset (n=172), PFS HR was 0.66 (0.459, 0.942) and OS HR was 0.51 (0.306, 0.860). The adverse event (AE) profile of MIRV was consistent with prior reports: predominantly low-grade ocular (MIRV vs IC all grade 56% vs 9%; grade 3+ 14% vs 0%) and gastrointestinal events (MIRV vs IC all grade 70% vs 66%; grade 3+ 13% vs 15%). Compared with IC, MIRV was associated with lower rates of grade 3+ treatment-emergent AEs (42% vs 54%), serious AEs (24% vs 33%), and discontinuations due to TEAEs (9% vs 16%). Fourteen percent of pts on the MIRV arm remained on study drug vs 3% on the IC arm. Conclusion: MIRV is the first treatment to demonstrate a PFS and OS benefit in PROC compared to IC. The efficacy data, along with the well-characterized safety profile, position MIRV as a new, standard of care for pts with FRα positive PROC. Clinical trial information: NCT04209855 .[Table: see text]
A randomised phase II multicentre study of ipilimumab with temozolomide vs temozolomide alone after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma: Ipi-Glio.
Authors: Paul James Mulholland, Nicholas Fraser Brown, Catherine McBain, Lucy Brazil, Sharon Peoples, Sarah Jefferies, Fiona Harris, Puneet Plaha, Anup Vinayan, Claire Brooks, Samia Hussain, Susan J. Dutton, Stasya Ng, Stephanie Levy, Timothy Coutts
Journal: Journal of Clinical Oncology (2023)

LBA2023 Background: Median survival for patients with glioblastoma is less than a year. Standard treatment comprises surgical debulking if feasible followed by temozolomide (TMZ) chemoradiotherapy. The objective of this clinical trial is to evaluate whether the addition of the CTLA-4 immune checkpoint inhibitor ipilimumab (IPI) improves survival. Methods: Ipi-Glio is an academic phase II, open label, stratified randomised multicentre study of IPI + TMZ (Arm A) vs TMZ alone (Arm B), after surgery and radical radiotherapy with concomitant temozolomide in patients with recently diagnosed de-novo glioblastoma. Following completion of chemoRT, patients were randomised 2:1 Arm A:B, with stratification to extent of surgery and MGMT promotor methylation. IPI 3mg/kg was administered q3/52 for 4 cycles, and TMZ 150-200mg/m2 days 1-5 q4/52 for 6 cycles. Primary outcome was overall survival (OS), treatment difference reported as hazard ratio (HR) with 60% confidence intervals (CI) and OS at 18 months. Secondary outcomes were progression-free Survival (PFS) and safety. Results: 119 patients were randomly assigned, 79 to Arm A and 40 to Arm B, at seven centres in the UK between Jan 2019 and April 2021. Patient characteristics (Arm A vs B): median Age 53 vs 48 years; male sex 70% vs 65%; ECOG PS0 70 vs 70%, PS1 30 vs 30%; MGMT promotor methylation 39% vs 40%; IDH mutation 11% vs 10%; surgical gross total resection 61% vs 60%. PFS (Arm A vs B): median PFS 10.9 months (m) vs 12.5mo, HR 1.252 (60%CI 1.01-1.54, p=0.369); 18m PFS 22% (60%CI 17-27%) vs 43% (34-51%). Overall Survival (Arm A vs B): median OS 22.7 vs 26.4 months, HR 1.223 (60% CI 0.986-1.516, p=0.431); 18 month OS 53% (60%CI 48-58%) vs 64% (56-70%). Adverse events (AE) reported by CTCAE grade (Arm A vs B): total reported AEs 1058 vs 329; no. of reported AEs per patient: mean 13.5 (SD 10.1) vs mean 8.2 (SD 7.3). Conclusions: No improvement in PFS or OS was observed with the addition of ipilimumab to temozolomide. This study does not support further investigation of this regimen in this setting. Clinical trial information: ISRCTN84434175 .
Dexamethasone and exercise for cancer-related fatigue: A phase III randomized controlled trial.
Authors: Vanita Noronha, Supriya Goud, Sarika Gautam Mahajan, Rangita Sharma, Akanksha Yadav, Akash Pawar, Sravan Kumar Chintala, Minit Jalan Shah, Sucheta Bhagwan More, Nandini Sharrel Menon, Vijay Maruti Patil, Ajaykumar Chandrabhan Singh, Srushti Shah, Kavita Prakash Nawale, Dipti Nakti, Anuradha Daptardar, Naveen Karuvandan, Laboni Sarkar, Mannavi Suman, Kumar Prabhash
Journal: Journal of Clinical Oncology (2023)

LBA12098 Background: Cancer-related fatigue (CRF) significantly impacts QoL of patients. Dexamethasone with physical activity may improve CRF. Methods: Phase III randomized study in patients with advanced cancer on palliative intent therapy, with ECOG PS 0-2, and fatigue score &gt; 4/10 on numeric rating scale. Intervention included oral dexamethasone 8 mg twice daily for 7 days, and exercise (aerobic + resistance). Results: From Dec 2022 to Feb 2023, we enrolled 114 pts; 56 in intervention arm, and 58 in standard arm. Median age was 56 yrs (IQR, 47.8 to 65), with 74 (64.9%) males. Common tumors were lung (75, 65.8%), head-and-neck (12, 11%), and breast (10, 8.8%). Compliance was 87.3% (n=48) for dexa, and 70.9% (n=39) for exercise. Primary endpoint of mean improvement in FACIT-Fatigue subscale on day 8 was 3.22 (SD, 12.69) in intervention, compared to 1.73 (SD, 9.97) in standard arm; P =0.495. However, 54.5% patients in intervention had at least 3 points (minimal clinically relevant) decrease in fatigue, vs 41.8% in control; P=0.182. By day 29, mean change in FACIT-Fatigue scores compared to baseline was similar in intervention vs control; 2.61 (SD, 14.64) vs 2.68 (SD, 12.87), respectively; P=0.978. Although overall symptoms (ESAS) and general QoL were similar, there was a significant improvement in fatigue symptom on EORTC QLQ-C30 in intervention on day 29 compared to baseline; P=0.013. Sleep quality also significantly improved on Day 29 in intervention; P=0.018. On EORTC-QLQ FA12 (cancer-related fatigue QoL), physical fatigue improved significantly from baseline to Day 8 in intervention versus control; P=0.035; with no difference in emotional or cognitive fatigue, interference with daily life, or social sequelae. There was no difference in grade ≥ 3 adverse events between groups; 18 (32.7%) in intervention group versus 18 (30.5%) in control group; P=0.799. Conclusions: Dexamethasone and exercise did not lead to a statistically significant improvement in fatigue by FACT-Fatigue scale, although it resulted in greater proportion of pts with clinically relevant improvements in fatigue. The intervention significantly improved QoL fatigue symptom score and reduced physical fatigue on QoL, along with improving sleep quality. Clinical trial information: CTRI/2022/09/045678 . [Table: see text]
Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma: 5-year analysis of KEYNOTE-426.
Authors: Brian I. Rini, Elizabeth R. Plimack, Viktor Stus, Rustem Gafanov, Tom Waddell, Dmitry Nosov, Frederic Pouliot, Boris Alekseev, Denis Soulieres, Bohuslav Melichar, Ihor O. Vynnychenko, Sergio Jobim Azevedo, Delphine Borchiellini, Raymond S. McDermott, Jens Bedke, Satoshi Tamada, Sterling Wu, Joseph Burgents, L. Rhoda Molife, Thomas Powles
Journal: Journal of Clinical Oncology (2023)

LBA4501 Background: At the first interim analysis of the randomized, open-label, phase 3 KEYNOTE-426 (NCT02853331) study, 1L pembro + axi showed statistically significant OS, PFS, and ORR over sun for advanced ccRCC. We report results with 5-y minimum follow-up. Methods: Adults with confirmed locally advanced or metastatic ccRCC with or without sarcomatoid features, no previous systemic therapy for metastatic ccRCC, KPS ≥70%, and ≥1 lesion measurable per RECIST v1.1 were randomly assigned 1:1 to receive pembro 200 mg IV Q3W for 35 doses (~2 y) + axi 5 mg PO BID or sun 50 mg PO QD on a 4-wk-on/2-wk-off schedule. Dual primary end points were OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary end points included ORR and DOR per RECIST v1.1 by BICR, and safety. A post hoc analysis adjusting for the effect of subsequent therapy on OS using a 2-stage adjustment model was conducted. Results: Of 861 enrolled patients (pts), 432 were assigned to pembro + axi and 429 to sun. Median study follow-up was 67.2 mo (range, 60.0-75.0). Efficacy for the ITT population and IMDC risk subgroups are shown in table. For pembro + axi vs sun, the 60-mo OS rates were 41.9% vs 37.1%, and the 60-mo PFS rates were 18.3% vs 7.3%. Median DOR (range) was 23.6 mo (1.4+ to 68.6+) for pembro + axi and 15.3 mo (2.3-68.3) for sun. In pts who discontinued treatment, 237/381 pts (62.2%) in the pembro + axi arm and 300/406 pts (73.9%) in the sun arm received subsequent anticancer treatment. The HR for OS when adjusted for subsequent therapy was 0.67 (95% CI, 0.52-0.84). Clinical data on pts who completed 2 y of pembro will be presented. No new safety signals were observed. Conclusions: After 5 y of follow-up, pembro + axi had sustained OS, PFS, and ORR benefits over sun in advanced ccRCC. These results are the longest follow-up to date of an anti–PD-1/L1 inhibitor + VEGFR TKI in this pt population and continue to support the use of pembro + axi as a 1L standard of care for advanced ccRCC. Clinical trial information: NCT02853331 .
Randomized phase II trial of cabozantinib combined with PD-1 and CTLA-4 inhibition versus cabozantinib in metastatic soft tissue sarcoma.
Authors: Brian Andrew Van Tine, Vanessa Eulo, Jacqui Toeniskoetter, Tyler Ruff, Jingqin Luo, Lindsey Kemp, Cristiam Moreno Tellez, Mia C. Weiss, Angela C. Hirbe, Christian Frederick Meyer, Anthony D. Elias, Mark Diamond, Lee P. Hartner, Nam Bui, Kristen N. Ganjoo, Robert G. Maki, Breelyn A. Wilky
Journal: Journal of Clinical Oncology (2023)

LBA11504 Background: Cabozantinib (C) has been combined successfully with either PD-1 or CTLA-4 inhibition in cancer clinical trials. The combination of nivolumab (N) and ipilimumab (I) previously was evaluated in soft tissue sarcoma (STS) and demonstrated activity as well as an acceptable safety profile. Given these data, we hypothesize that C in combination with both I and N is a therapeutic strategy that will be more effective than C alone in metastatic STS that lack translocations. Additionally, we hypothesized that C priming would enhance the efficacy of combination I and N at the time of crossover. Methods: This is a 2:1 randomized phase 2 clinical trial evaluating the overall response rate (RR) of C 40mg orally daily in combination with I (1mg/kg IV) / N (3mg/kg) for 4 doses Q3W and then maintenance N 480mg Q4W compared to C 60mg oral alone, with crossover. Secondary endpoints include progression free survival (PFS), disease control rate (DCR), RR in crossover, quality of life by FACT-G7, RR by iRECIST and safety. Correlative and biomarker analysis are preplanned. Key patient selection includes ECOG 0-1, 1-2 lines of prior therapy, and sarcomas that lack of translocations. The trial was balanced for leiomyosarcoma (LMS), liposarcoma and UPS. Results: 69 patients were randomized to C+I/N and 36 patients were randomized to C alone. 19 patients crossed over to C+I/N at progression. 54/105 patients had LMS. RR of C+I/N was 11% (5 PR and 2 CR), while the RR of C was 6% (2 PR and 0 CR) (p = NS). C+I/N responding histologies included LMS, angiosarcoma, epithelioid sarcoma, and myxofibrosarcoma. C responding histologies included 2 PRs in LMS. There were also 2 LMS PRs in crossover to C+I/N. The median PFS for C+I/N was 5.4 months and for C was 3.8 months (p = 0.016). The DCR for C+I/N was 80% (41 SD, 5 PR, 2 CR), and 42% for C (11 SD, 2 PR) (p = 0.0004). The most common grade 3-4 adverse events affecting &gt; 10% of patients included hypothyroidism, diarrhea, mucositis, oral dysesthesia, nausea, vomiting, elevated AST and ALT, anorexia, dysgeusia, headache, pruritis, maculopapular rash, and hypertension for C+I/N and hypothyroidism, diarrhea, oral dysesthesia, fatigue, palmar-plantar erythrodysesthesia, and hypertension for C. Conclusions: The combination of C+I/N was superior to C for the treatment of non-translocation STS for DCR and PFS. Most frequent responding histology was LMS. Correlative work is ongoing. Clinical trial information: NCT04551430 .
TORCHLIGHT: A randomized, double-blind, phase III trial of toripalimab versus placebo, in combination with nab-paclitaxel(nab-P) for patients with metastatic or recurrent triple-negative breast cancer (TNBC).
Authors: Zefei Jiang, Quchang Ouyang, Tao Sun, Qingyuan Zhang, Yuee Teng, Jiuwei Cui, Haibo Wang, Yongmei Yin, Xiaojia Wang, Xin Zhou, Yongsheng Wang, Gang Sun, Jingfen Wang, Lili Zhang, Jin Yang, Jun Qian, Tienan Yi, Min Yan, Xinlan Liu
Journal: Journal of Clinical Oncology (2023)

LBA1013 Background: Checkpoint blockade combined with taxanes based chemotherapy had generated mixed results as first line treatment for metastatic TNBC. Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, provided significant clinical efficacy with a favorable safety profile in various solid tumors. The purpose of this study is to compare the efficacy and safety of toripalimab versus placebo, in combination with nab-P for metastatic or recurrent TNBC (NCT04085276). Methods: Patients with initially diagnosed metastatic or recurrent inoperable TNBC were randomized 2:1 to receive toripalimab (240mg, D1, q3w) or placebo along with nab-P on days1, 8 in 3-week cycles. Stratifications included PD-L1 expression, paclitaxel therapy history and line of prior therapy at enrollment. Primary endpoint was progression-free survival (PFS) assessed by a blinded independent central review (BICR) per RECIST v1.1, first in the PD-L1-positive population and then in the ITT population. Secondary endpoints included overall survival (OS) and safety. Results: 531 patients were randomized to toripalimab (n = 353) or placebo (n = 178); 200 and 100 patients, respectively had PD-L1 positive TNBC. At interim analysis, with the median follow-up of 14 months, a statistically significant improvement in PFS by BICR was demonstrated for the toripalimab arm in the PD-L1 positive subgroup (mPFS 8.4 vs 5.6 months; HR = 0.653, 95% CI 0.470-0.906, P = 0.0102). The PFS in the ITT population showed a similar trend (mPFS 8.4 vs 6.9 months, HR = 0.773, 95%CI 0.602-0.994). Descriptive analysis of OS showed a trend towards improved OS in the PD-L1 positive (mOS 32.8 vs 19.5 months; HR = 0.615, 95%CI 0.414-0.914) and the ITT population (mOS 33.1 vs 23.5 months; HR = 0.691, 95% CI 0.513-0.932). No new safety signals were identified. Grade≥3 adverse events (AEs) (56.4% vs 54.3%) and fatal AEs (0.6% vs 3.4%) were similar between arms, while AEs leading to discontinuation of toripalimab/placebo (8.5% vs. 3.4%) and immune-related (irAEs) (40.8% vs. 24.0%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to nab-P provided a significant improvement in PFS for PD-L1 positive metastatic or recurrent TNBC patients receiving first-line treatment with an acceptable safety profile. Patients will be followed for the final PFS and OS analysis. Clinical trial information: NCT04085276 .
Efficacy and safety of atezolizumab plus cabozantinib vs cabozantinib alone after progression with prior immune checkpoint inhibitor (ICI) treatment in metastatic renal cell carcinoma (RCC): Primary PFS analysis from the phase 3, randomized, open-label CONTACT-03 study.
Authors: Toni K. Choueiri, Laurence Albiges, Piotr Tomczak, Cristina Suárez, Martin H. Voss, Guillermo de Velasco, Jad Chahoud, Giuseppe Procopio, Hakim Mahammedi, Friedemann Zengerling, Chan Kim, Suyasha Gupta, Guillaume Bergthold, Bo Liu, Melania Kalaitzidou, Mahrukh A. Huseni, Christian Scheffold, Thomas Powles, Sumanta Kumar Pal
Journal: Journal of Clinical Oncology (2023)

LBA4500 Background: ICI-based regimens are the standard of care for first-line (1L) treatment of metastatic clear cell (cc) RCC. Treatment options following disease progression during or after ICI therapy are limited but can include single-agent TKIs, such as cabozantinib (cabo). CONTACT-03 evaluated anti–PD-L1 atezolizumab (atezo) + cabo vs cabo alone in patients (pts) with metastatic RCC that progressed during or after prior ICI treatment and is the first phase 3 randomized trial to test the benefit of ICI rechallenge by direct addition to a control arm. Methods: CONTACT-03 enrolled pts with histologically confirmed, inoperable, locally advanced or metastatic cc or non-cc RCC, regardless of PD-L1 status, that progressed on or after ICI treatment. Randomization was 1:1 to atezo (1200 mg IV q3w) plus cabo (60 mg oral qd) or cabo alone. Stratification factors were IMDC risk factors (0 vs 1-2 vs ≥3); most recent line of prior ICI therapy (adjuvant vs 1L vs 2L); and histology (dominant cc without sarcomatoid vs dominant non-cc [papillary or unclassified] without sarcomatoid vs cc or non-cc with any sarcomatoid component). The multiple primary efficacy endpoints were centrally reviewed RECIST 1.1 PFS and OS. Key secondary endpoints were investigator (INV)-assessed PFS, centrally reviewed RECIST 1.1 ORR and DOR and safety. Results: Of 522 pts randomized to atezo + cabo (n=263) or cabo (n=259), 55% and 51% had most recent ICI in the 1L setting and 10% and 11% had sarcomatoid RCC, respectively. At the data cutoff (Jan 3, 2023), median follow-up was 15.2 mo. No PFS or OS benefit was observed with atezo + cabo vs cabo. ORR was 41% in both arms; DOR was 12.7 (95% CI: 10.5, 17.4) mo with atezo + cabo and 14.8 (95% CI: 11.3, 20.0) mo with cabo. All-cause Grade 3/4 adverse events (AEs) occurred in 68% (177/262) and 62% (158/256) of safety-evaluable pts receiving atezo + cabo or cabo, respectively; all-cause Grade 5 AEs occurred in 6% and 4%. AEs leading to treatment withdrawal occurred in 16% of pts on atezo + cabo and 4% on cabo. Conclusions: The addition of atezo to cabo did not improve clinical outcomes and led to increased toxicity in patients with RCC that progressed on or after prior ICI treatment. CONTACT-03 is the first randomized, phase III oncology trial to test the benefit of PD-(L)1 inhibitor continuation by direct addition to a standard control arm; the results prompt caution with this approach in other cancers. Clinical trial information: NCT04338269 . [Table: see text]
PROSPECT: A randomized phase III trial of neoadjuvant chemoradiation versus neoadjuvant FOLFOX chemotherapy with selective use of chemoradiation, followed by total mesorectal excision (TME) for treatment of locally advanced rectal cancer (LARC) (Alliance N1048).
Authors: Deborah Schrag, Qian Shi, Martin R. Weiser, Marc J Gollub, Leonard B. Saltz, Benjamin Leon Musher, Joel Goldberg, Tareq Al Baghdadi, Karyn A. Goodman, Robert R. McWilliams, Jeffrey M. Farma, Thomas J. George, Hagen Fritz Kennecke, Alan P. Venook, Eileen Mary O'Reilly, Jeffrey A. Meyerhardt, Amylou C. Dueck, Ethan Basch, George J. Chang, Harvey J. Mamon
Journal: Journal of Clinical Oncology (2023)

LBA2 Background: Radiation with sensitizing fluoropyrimidine (5FUCRT) is a standard curative intent treatment for LARC. It improves disease-free survival (DFS) by decreasing pelvic recurrence but has short- and long-term toxicity. The PROSPECT trial compares FOLFOX chemotherapy with selective use of 5FUCRT (intervention) to 5FUCRT (control) for neoadjuvant treatment prior to TME for LARC. Methods: Eligible patients (pts) had cT2N+, cT3N-, cT3N+ rectal cancers deemed appropriate for neoadjuvant therapy prior to low anterior resection with TME. Pts with distal, T4 tumors, threatened radial margins or &gt; 4 enlarged lymph nodes were ineligible. Pts were randomized 1:1 without blinding. Pts in the control group received 5FUCRT with 5040 cGy over 5.5 weeks with either capecitabine or 5FU. Pts in the intervention group had 6 cycles of mFOLFOX6 followed by restaging. If tumor regression was &gt; 20%, then TME was performed without radiation; if &lt; 20%, 5FUCRT was given before TME. DFS was the 1°outcome, defined as time from randomization to any recurrence or death, analyzed in the per-protocol population. One interim analysis was conducted with α spending = 0.001. Noninferiority (NI) of the intervention could be claimed if the upper limit of the 2-sided 90.2% confidence interval (CI) of the DFS hazard ratio did not exceed 1.29 (NI margin). Secondary endpoints included overall survival (OS), local recurrence free survival, R0 resection, pathologic complete response (CR), and toxicity. Results: From June 2012 to December 2018, 1194, pts were randomized and 1128 initiated protocol-assigned treatment. Median age was 57, 34.5% were women and 61.9% had clinically positive nodes. 53 of 585 pts in the intervention group (9%) received preop 5FUCRT. DFS was analyzed after 227 events and median follow-up of 58 months. Conclusions: FOLFOX chemotherapy with selective use of 5FUCRT is non-inferior to 5FUCRT for neoadjuvant treatment of LARC prior to low anterior resection with TME. Patients and physicians have alternative strategies for management of LARC. Clinical trial information: NCT01515787 . [Table: see text]